Cerulean Pharma has dosed first patient in a Phase 1b / 2a study of the investigational anti-cancer agent, CRLX101, in combination with Avastin in metastatic renal cell carcinoma (mRCC) patients whose disease has progressed following treatment with at least one prior molecularly targeted therapy.
CRLX101, a dual inhibitor of topoisomerase 1 and hypoxia-inducible factor-1 alpha, is a dynamically tumour-targeted nanopharmaceutical designed to concentrate on tumours, prolonging drug exposure at the site of action.
The study principal investigator, Stephen Keefe, said the new trial for patients with RCC will assist in discovering whether CRLX101 is synergistic with Avastin, the leading VEGF inhibitor.
"We are excited about the potential efficacy of combining these two agents, which mechanistically reinforce each other. The benefit of this approach – attacking multiple targets at once – is not limited to RCC, however, and could be applicable in other cancers as well," Keefe added.
The study incorporates a rapid dose escalation stage and a subsequent efficacy stage to evaluate the activity of CRLX101.
The trial is being conducted at the Abramson Cancer Center of the University of Pennsylvania, according to the company.
Cerulean chief medical officer, Edward Garmey, said the company had observed that the intratumour pharmacokinetic properties of nanopharmaceuticals can lead to novel pharmacodynamic effects.
"We will be collaborating with Dr Keefe and his colleagues to assess the impact of CRLX101 on HIF-1 alpha, an exciting oncology drug target that appears to be widely upregulated in hypoxic conditions and in RCC," Garmey added.
Image: Renal cell carcinoma. Photo courtesy of: Ed Uthman, MD.